The long-term objective of this project is the development and characterization of a conjugate between human urokinase and a monoclonal antibody (or antigen-binding fragment) specific for human fibrin. This complex would allow for enhanced plasminogen activation at the sites of fibrin clots while reducing systemic activation of plasminogen and the associated deleterious effects. The initial goal of these studies will be to examine the immunochemistry of human fibrin and fibrinogen, using polyclonal rabbit antiserum to human fibrin and extensive absorbtion with human fibrinogen, with the objective of finding epitopes unique to fibrin. Secondly, the plasminogen activating activity of human urokinase that has been covalently coupled to polyclonal rabbit anti-human fibrinogen will be investigated. Standard coupling procedures will be employed, and the antigenic specificity, enzymatic activity, and susceptibility to protease inhibitors of the resulting complexes will be determined. In addition to potential development of an improved thrombolytic agent for clinical use, these studies may lead to the development of a more general approach for targeting specific enzymes to pathological sites.